WO2023063322A1 - Agent pour la prévention, le traitement ou l'atténuation d'une maladie inflammatoire de la peau - Google Patents

Agent pour la prévention, le traitement ou l'atténuation d'une maladie inflammatoire de la peau Download PDF

Info

Publication number
WO2023063322A1
WO2023063322A1 PCT/JP2022/037897 JP2022037897W WO2023063322A1 WO 2023063322 A1 WO2023063322 A1 WO 2023063322A1 JP 2022037897 W JP2022037897 W JP 2022037897W WO 2023063322 A1 WO2023063322 A1 WO 2023063322A1
Authority
WO
WIPO (PCT)
Prior art keywords
mass
content
diacylglycerol
linolenic acid
barrier function
Prior art date
Application number
PCT/JP2022/037897
Other languages
English (en)
Japanese (ja)
Inventor
慧門 佐山
聡子 深川
准子 石川
綾 佐々木
Original Assignee
花王株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 花王株式会社 filed Critical 花王株式会社
Priority to EP22881017.2A priority Critical patent/EP4417200A1/fr
Priority to CN202280068545.9A priority patent/CN118119388A/zh
Publication of WO2023063322A1 publication Critical patent/WO2023063322A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS, COOKING OILS
    • A23D9/00—Other edible oils or fats, e.g. shortenings, cooking oils
    • A23D9/007—Other edible oils or fats, e.g. shortenings, cooking oils characterised by ingredients other than fatty acid triglycerides
    • A23D9/013—Other fatty acid esters, e.g. phosphatides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/08—Antiseborrheics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Definitions

  • the present invention relates to preventive, therapeutic or ameliorating agents for inflammatory skin diseases such as atopic dermatitis.
  • Atopic dermatitis is one of the skin diseases accompanied by inflammation, which is caused by genetic and environmental factors. Recent studies have revealed that the pathogenesis of atopic dermatitis involves both immunological abnormalities and defects in skin barrier function.
  • the barrier function of the skin is mainly borne by the stratum corneum and the sebum membrane that covers its surface, and when they function normally, it prevents water loss from the body and prevents the entry of various stimuli and substances from the outside world.
  • ⁇ -Linolenic acid (C18:3, ALA) is a ⁇ 3 highly unsaturated fatty acid that is abundantly contained in linseed oil and perilla seed oil. ⁇ -Linolenic acid is reported to have antiarteriosclerotic, hypertensive, and antiallergic effects. In addition, it has been reported that ingestion of linseed oil improves the value of transepidermal water loss (TEWL) in dry and sensitive skin (Non-Patent Document 1). On the other hand, it has been reported that fats and oils containing a high concentration of diacylglycerol suppress the increase in blood triglycerides (neutral fats) after meals and have physiological effects such as less accumulation in the body.
  • TEWL transepidermal water loss
  • Patent Document 1 15 to 90% by weight of the constituent fatty acids are ⁇ 3 unsaturated fatty acids with less than 20 carbon atoms, and cis ⁇ 3 unsaturated fatty acids / (cis ⁇ 6 unsaturated fatty acids + saturated fatty acids + trans It is reported that a fat composition containing 60 to 100% by weight of diglyceride with a weight ratio of 1 to 6 (unsaturated fatty acid) is excellent in visceral fat burning property and body fat burning property. However, it is not known that diacylglycerol-containing fats and oils containing a large amount of ⁇ -linolenic acid as a constituent fatty acid are useful for preventing or treating inflammatory skin diseases such as atopic dermatitis.
  • Patent Document 1 JP-A-2002-138296
  • Non-Patent Document 1 Jean-Marc Maurette. OCL. 2008, 15(4), 257-261
  • the present invention relates to the following 1) to 12).
  • oils and fats that are above.
  • the content of ⁇ -linolenic acid in fatty acids constituting fats and oils is 40% by mass or more and the content of diacylglycerol is 25% by mass or more, for use in the prevention, treatment or improvement of inflammatory skin diseases. oils and fats.
  • the content of ⁇ -linolenic acid in fatty acids constituting fats and oils is 40% by mass or more and the content of diacylglycerol is 25% by mass or more for the prevention, treatment or improvement of inflammatory skin diseases.
  • AD dermatitis score
  • TEWL transepidermal water loss
  • the present invention relates to providing a preventive, therapeutic or ameliorating agent for inflammatory skin diseases.
  • the present inventors used atopic dermatitis model mice to evaluate the effectiveness of diacylglycerol-containing fats and oils rich in ⁇ -linolenic acid.
  • the dermatitis score and the thickening of the auricle were suppressed, the increase in transepidermal water loss (TEWL) was suppressed, and the increase in various cytokines related to inflammatory skin diseases was suppressed. is useful for prevention or treatment of inflammatory skin diseases such as atopic dermatitis.
  • pharmaceuticals, foods, etc. are provided that are effective in preventing, treating, or improving inflammatory skin diseases by suppressing dermatitis and improving skin barrier function.
  • fat refers to an ester compound of fatty acid and glycerin, and includes any one or more of monoacylglycerol, diacylglycerol and triacylglycerol. There are no particular restrictions on the type of fat and oil, and any fat or oil that can be used as an edible fat or oil may be used.
  • the fats and oils used in the present invention are those in which the content of ⁇ -linolenic acid in the fatty acids constituting the fat is 40% by mass or more and the content of diacylglycerol is 25% by mass or more.
  • fat and oil in which the content of ⁇ -linolenic acid in the fatty acid constituting the fat is 40% by mass or more and the content of diacylglycerol is 25% by mass or more is simply referred to as “the fat of the present invention. ” may be stated.
  • the content of ⁇ -linolenic acid in the fatty acids constituting the fats and oils of the present invention is 40% by mass or more, preferably 45% by mass or more, more preferably 50% by mass or more, and still more preferably from the viewpoint of physiological effects. It is 52% by mass or more, and from the viewpoint of oxidation stability, it is preferably 80% by mass or less, more preferably 70% by mass or less, and even more preferably 60% by mass or less.
  • the content of ⁇ -linolenic acid in fatty acids constituting fats and oils is 40% by mass or more and 80% by mass or less, preferably 45% by mass or more and 80% by mass or less, more preferably 50% by mass or more and 80% by mass or less, and more preferably.
  • the fatty acid amount in this specification is a free fatty acid conversion amount.
  • the constituent fatty acids other than ⁇ -linolenic acid that constitute fats and oils are not particularly limited, and may be either saturated fatty acids or unsaturated fatty acids.
  • the content of unsaturated fatty acids in the fatty acids constituting the oils is preferably 60% by mass or more and 100% by mass or less, more preferably 70% by mass or more and 100% by mass or less. , more preferably 75% by mass or more and 99% by mass or less, more preferably 80% by mass or more and 98% by mass or less.
  • the number of carbon atoms in the unsaturated fatty acid is preferably 14-24, more preferably 16-22, from the viewpoint of physiological effects.
  • the content of linoleic acid (C18:2) in fatty acids constituting fats and oils is preferably 5% by mass or more, more preferably 10% by mass or more, from the viewpoint of industrial productivity. Therefore, it is preferably 40% by mass or less, more preferably 30% by mass or less, and still more preferably 20% by mass or less.
  • the content of linoleic acid (C18:2) in fatty acids constituting fats and oils is preferably 5% by mass or more and 40% by mass or less, more preferably 10% by mass or more and 30% by mass or less, and still more preferably 10% by mass. It is more than 20 mass % or less.
  • the content of oleic acid (C18:1) in fatty acids constituting fats and oils is preferably 10% by mass or more from the viewpoint of industrial productivity, and preferably 50% by mass from the viewpoint of physiological effects. % or less, more preferably 40 mass % or less, and still more preferably 30 mass % or less.
  • the content of oleic acid (C18:1) in fatty acids constituting fats and oils is preferably 10% by mass or more and 50% by mass or less, more preferably 10% by mass or more and 40% by mass or less, and still more preferably 10% by mass. It is more than 30 mass % or less.
  • the total content of saturated fatty acids in fatty acids constituting fats and oils is preferably 6.0% by mass or less, more preferably 5.5% by mass or less, from the viewpoint of appearance, physiological effects, and industrial productivity of fats and oils. Preferably, it is 5.0% by mass or less. Moreover, from the point of industrial productivity, it is preferably 0.5% by mass or more.
  • the total content of saturated fatty acids in fatty acids constituting fats and oils is preferably 0.5% by mass or more and 6.0% by mass or less, more preferably 0.5% by mass or more and 5.5% by mass or less, and still more preferably 0%. .5% by mass or more and 5.0% by mass or less.
  • the type of saturated fatty acid is not particularly limited, saturated fatty acids with 14 to 24 carbon atoms are preferred, saturated fatty acids with 16 to 22 carbon atoms are more preferred, and saturated fatty acids with 16, 18 and 20 carbon atoms are even more preferred.
  • the content of diacylglycerol in the oil and fat of the present invention is 25% by mass or more, but from the viewpoint of effective expression of the effect and physiological effect, it is preferably 30% by mass or more, more preferably 50% by mass or more.
  • the content of diacylglycerol in the oil is preferably 25% by mass or more and 96% by mass or less, more preferably 30% by mass or more and 96% by mass or less, still more preferably 50% by mass or more and 96% by mass or less, still more preferably 50% by mass.
  • % or more and 95 mass % or less more preferably 55 mass % or more and 95 mass % or less, more preferably 60 mass % or more and 95 mass % or less, still more preferably 65 mass % or more and 95 mass % or less, still more preferably 65 mass % or more 94% by mass or less, more preferably 70% by mass or more and 94% by mass or less, more preferably 80% by mass or more and 94% by mass or less, still more preferably 83% by mass or more and 94% by mass or less, still more preferably 84% by mass or more and 94% by mass % or less.
  • the fatty acid that constitutes diacylglycerol may be either a saturated fatty acid or an unsaturated fatty acid. It is preferable from the point of exhibiting an effect effectively.
  • the content of ⁇ -linolenic acid in the fatty acid constituting diacylglycerol is preferably 45% by mass or more, more preferably 50% by mass or more, and still more preferably 52% by mass or more. From the viewpoint of stability, the content is preferably 80% by mass or less, more preferably 70% by mass or less, and even more preferably 60% by mass or less.
  • the content of ⁇ -linolenic acid in the fatty acid constituting diacylglycerol is 40% by mass or more and 80% by mass or less, preferably 45% by mass or more and 80% by mass or less, more preferably 50% by mass or more and 80% by mass or less, and more It is preferably 50% by mass or more and 70% by mass or less, more preferably 52% by mass or more and 70% by mass or less, and still more preferably 52% by mass or more and 60% by mass or less.
  • the fats and oils of the present invention may contain triacylglycerol, and the content thereof is preferably 1% by mass or more, more preferably 2% by mass or more, and still more preferably It is 5% by mass or more, and preferably 75% by mass or less, more preferably 72% by mass or less, more preferably 50% by mass or less, and more preferably 25% by mass or less.
  • the content of triacylglycerol in fats and oils is preferably 1% by mass or more and 75% by mass or less, more preferably 2% by mass or more and 75% by mass or less, still more preferably 2% by mass or more and 72% by mass or less, still more preferably 5% by mass or more.
  • the content of monoacylglycerol in fats and oils is preferably 3% by mass or less, more preferably 2% by mass or less, still more preferably 1.51% by mass, from the viewpoint of flavor and industrial productivity of fats and oils. or less, and preferably more than 0% by mass.
  • the content of monoacylglycerol in fats and oils may be 0% by mass. From the viewpoint of industrial productivity of fats and oils, it is preferable that the triacylglycerol, diacylglycerol and monoacylglycerol have the same fatty acid composition.
  • the fats and oils of the present invention may contain free fatty acids or salts thereof as impurities.
  • the content of free fatty acids or salts thereof in fats and oils is preferably 3% by mass or less, more preferably 2% by mass or less, still more preferably 1% by mass or less, and preferably 0% by mass, from the viewpoint of flavor.
  • the content of free fatty acids or salts thereof in fats and oils may be 0% by mass.
  • the fats and oils of the present invention can be obtained by an esterification reaction between fatty acids derived from fats and oils and glycerin, a transesterification reaction (glycerolysis) between fats and oils and glycerin, and the like. Ordinary edible oils and fats may be mixed as necessary.
  • the esterification reaction and the glycerolysis reaction can be performed by chemical methods using chemical catalysts such as alkali metals or their alloys, oxides and hydroxides of alkali metals or alkaline earth metals, alkoxides of alkali metals or alkaline earth metals, and lipases. enzymatic method using the enzyme of Among them, from the viewpoint of controlling the fatty acid composition, an esterification reaction between a fatty acid (fractionated fatty acid) obtained by hydrolyzing fats and oils described below and glycerin is preferable.
  • the origin of the fat is not particularly limited as long as it can be used as an edible fat, and may be either vegetable fat or animal fat.
  • oils and fats can include oils and fats. These oils may be used alone, or may be used by appropriately mixing them. Among them, from the viewpoint of usability, it is preferable to use vegetable oils and fats, and it is preferable to use liquid oils and fats that are excellent in low temperature resistance. It is preferable to use two or more types of fats and oils because they contain abundant amounts of ⁇ -linolenic acid. Liquid fats and oils refer to fats and oils that are liquid at 20° C. when a cooling test according to the standard fat analysis test method 2.3.8-27 is carried out. Moreover, the edible fat is preferably a refined fat that has undergone a refining process.
  • Oil-derived fatty acids can be obtained by hydrolyzing fats and oils.
  • Methods for hydrolyzing fats and oils include a high-temperature high-pressure decomposition method and an enzymatic decomposition method.
  • the high-temperature and high-pressure cracking method is a method for obtaining fatty acids and glycerin by adding water to fats and oils and reacting them under high temperature and high pressure conditions.
  • the enzymatic decomposition method is a method of obtaining fatty acids and glycerin by adding water to fats and oils and reacting them under low temperature conditions using fat hydrolase as a catalyst.
  • a hydrolysis reaction can be performed according to a conventional method.
  • Fractionation methods include solvent fractionation, natural fractionation (dry fractionation), and wetting agent fractionation.
  • Means for removing the precipitated solid include static separation, filtration, centrifugal separation, and a method of mixing and separating the fatty acid with an aqueous wetting agent solution.
  • the esterification reaction between fatty acids derived from fats and oils and glycerin is preferably carried out under mild conditions by an enzymatic method because it is excellent in terms of flavor and the like.
  • the amount of enzyme to be used can be appropriately determined in consideration of the activity of the enzyme, but in the case of using an immobilized enzyme, from the viewpoint of improving the reaction rate, it is preferably is 1 to 30% by mass, more preferably 2 to 20% by mass.
  • the reaction temperature for the esterification reaction is preferably 0 to 100°C, more preferably 20 to 80°C, still more preferably 30 to 60°C, from the viewpoints of improving the reaction rate and suppressing deactivation of the enzyme.
  • the reaction time is preferably 15 hours or less, more preferably 1 to 12 hours, still more preferably 2 to 10 hours, from the viewpoint of industrial productivity.
  • means for contacting the fatty acid and glycerin include immersion, stirring, and passing through a column filled with immobilized lipase using a pump or the like.
  • a purification process that is usually used for fats and oils may be performed. Specifically, steps such as distillation treatment, acid treatment, washing with water, decolorization, and deodorization can be mentioned.
  • the dermatitis score representing the degree of progression of atopic dermatitis and the thickening of the auricle are suppressed, and transepidermal water transpiration is suppressed. (TEWL) increase was inhibited.
  • mRNA expression analysis in the skin at the dermatitis-induced site showed that IL-4, a major Th2 cytokine, and cytokines secreted from innate immune cells and keratinocytes were observed in the group ingested with the oil of the present invention.
  • IL-1 ⁇ , IL-6, TSLP, and IL-33 expression were suppressed.
  • the cytokine whose expression elevation is suppressed by the oil of the present invention can be used not only for atopic dermatitis but also for various inflammatory skin diseases such as seborrheic dermatitis, contact dermatitis, psoriasis, sebaceous eczema, and erythema nodosum. It has been reported that it contributes to the deterioration of the inflammatory response and barrier function in diseases (reference; Adalsteinsson JA, Kaushik S, et al. Exp Dermatol. 2020 May;29(5):481-489, Lee HY 2013;2013:916497, Belge K, et al. F1000Prime Rep.
  • the fats and oils of the present invention can be an agent for preventing, treating or improving inflammatory skin diseases, an agent for improving skin barrier function (hereinafter also referred to as "an agent for preventing, treating or improving inflammatory skin diseases, etc.”), It can be used to prevent, treat or improve skin diseases, improve skin barrier function, and can be used to produce agents for preventing, treating or improving inflammatory skin diseases.
  • "use" can be use in humans or non-human animals, and can be therapeutic or non-therapeutic.
  • Non-therapeutic means not including medical procedures, i.e., methods of surgery, treatment or diagnosis of humans, and more specifically, medical practitioners or persons under the direction of a physician It is a concept that does not include a method of performing surgery, therapy or diagnosis on a patient.
  • inflammatory skin diseases examples include atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, sebaceous eczema, erythema nodosum, neonatal acne, Acne-like rash, eczema, folliculitis, baby eczema, dry skin and the like. Among them, it is suitable for atopic dermatitis.
  • Atopic dermatitis refers to a chronic disease whose main lesion is itchy eczema with repeated exacerbations and remissions.
  • Skin barrier function means the function of preventing moisture from evaporating from the inside of the skin and the function of preventing substances from entering the skin from the outside.
  • the present invention is suitable for improving the function of preventing evaporation of water from the inside of the skin (moisture permeation barrier function). Improving the skin barrier function makes it possible to treat or improve xerosis (deficiency of sebum), deficient sebaceous eczema, etc. caused by a decrease in skin barrier function.
  • Prevention refers to preventing or delaying the onset of a disease or condition in an individual or reducing an individual's risk of developing a disease or condition.
  • “Amelioration” refers to amelioration of a disease, symptom or condition, prevention or delay of worsening of a disease, symptom or condition, or reversal, prevention or delay of progression of a disease or condition.
  • treatment includes amelioration of symptoms in addition to complete cure of disease.
  • the prophylactic, therapeutic or ameliorating agent for inflammatory skin diseases of the present invention itself can be used as pharmaceuticals, quasi-drugs, cosmetics, drugs for improving skin barrier function, for the prevention, treatment or improvement of inflammatory skin diseases. It can be a food or feed, and can be a material or formulation used by being mixed with the drug, quasi-drug, cosmetic, food, or feed.
  • the pharmaceuticals (including quasi-drugs, hereinafter the same) contain the oil of the present invention as an active ingredient for preventing, treating or improving inflammatory skin diseases and improving skin barrier function.
  • the drug may contain a pharmaceutically acceptable carrier or other active ingredient, pharmacological ingredient, etc., as necessary, as long as the function of the active ingredient is not lost.
  • the medicament can be administered in any dosage form. Dosage forms include, for example, tablets (including chewable tablets), capsules, granules, powders, oral solid formulations such as lozenges, oral liquid formulations, oral liquid formulations such as syrups, injections, suppositories, and inhalation. Examples include parenteral preparations such as drugs, percutaneous absorption agents, and external preparations.
  • a preferred mode of administration is oral administration.
  • the size of the form can be arbitrarily adjusted according to the purpose of use.
  • Formulations of such various dosage forms may optionally contain pharmaceutically acceptable carriers such as excipients, binders, fillers, disintegrants, surfactants, lubricants, dispersants, Buffers, osmotic pressure adjusters, pH adjusters, emulsifiers, preservatives, stabilizers, preservatives, thickeners, fluidity improvers, flavoring agents, foaming agents, fragrances, coating agents, diluents, etc. It can be prepared according to a conventional method by appropriately combining with the medicinal ingredients of
  • the cosmetic contains the oil of the present invention as an active ingredient for preventing or improving inflammatory skin diseases and improving skin barrier function. Furthermore, the cosmetics may contain carriers acceptable for cosmetics, or other active ingredients, medicinal ingredients, cosmetic ingredients, etc., as necessary, as long as the functions of the active ingredients are not lost.
  • Preferred examples of cosmetics containing the oil of the present invention include face and body cosmetics (e.g., lotions, gels, creams, packs, etc.), make-up cosmetics, face or body cleansers, and the like. . Each formulation of such cosmetics can be manufactured according to a conventional method.
  • Examples of carriers acceptable for cosmetics include various oils, surfactants, gelling agents, buffers, preservatives, antioxidants, solvents, dispersants, chelating agents, thickeners, ultraviolet absorbers, emulsifiers, Stabilizers, pH adjusters, pigments, fragrances, and the like can be mentioned.
  • Other active ingredients, medicinal ingredients, and cosmetic ingredients include, for example, plant extracts, bactericides, moisturizers, anti-inflammatory agents, antibacterial agents, keratolytic agents, cooling agents, antiseborrheic agents, cleansers, and makeup ingredients. etc.
  • the food contains the oil of the present invention as an active ingredient for preventing or improving inflammatory skin diseases and improving skin barrier function.
  • Foods that claim to prevent or improve the symptoms of inflammatory skin diseases or improve the skin barrier function, and for which labeling to that effect has been permitted or notified as necessary foods for specified health use, functional labeled foods, foods for special dietary uses, etc.). Examples of indications include "helps to retain moisture in the skin and has the function of relieving dryness", "have the function of alleviating skin discomfort", and the like.
  • Foods for which function labeling has been permitted or notified can be distinguished from ordinary foods.
  • the form of food can be solid, semi-solid or liquid (eg beverage).
  • Examples include various food compositions (breads, cakes, noodles, confectionery, frozen foods, ice creams, candies, sprinkles, soups, dairy products, shakes, beverages, seasonings, etc.), and further , and nutritional supplement compositions in the same form as the above-described oral administration formulations (solid formulations such as granules, powders, tablets, capsules, microcapsules, and lozenges).
  • Foods in various forms can be used in the present invention to add oils and fats to any food material, or other active ingredients, or additives acceptable for foods (e.g., solvents, softeners, oils, emulsifiers, preservatives, acidulants, Sweeteners, bittering agents, pH adjusters, stabilizers, colorants, UV absorbers, antioxidants, humectants, thickeners, sticking agents, dispersants, fluidity improvers, wetting agents, fragrances, seasonings , flavor modifier), etc., and can be prepared according to a conventional method.
  • solvents, softeners, oils, emulsifiers preservatives, acidulants, Sweeteners, bittering agents, pH adjusters, stabilizers, colorants, UV absorbers, antioxidants, humectants, thickeners, sticking agents, dispersants, fluidity improvers, wetting agents, fragrances, seasonings , flavor modifier), etc.
  • the feed contains the oil of the present invention as an active ingredient for preventing or improving inflammatory skin diseases and improving skin barrier function.
  • the form of feed is preferably in the form of pellets, flakes, mash, or liquid. Examples include feed, pet food used for dogs, cats, small birds, and the like.
  • the feed contains the oil and fat of the present invention and other feed materials such as meat, protein, grains, rice bran, lees, sugars, vegetables, vitamins, minerals, gelling agents, shape retention agents, and pH adjusters. , seasonings, preservatives, nutritional supplements, etc., and can be prepared according to a conventional method.
  • the content of the fats and oils of the present invention in the formulation cannot be generalized because it varies depending on the form of the formulation. It is 99.8% by mass or less.
  • the dosage or amount of the oil or fat used in the present invention can be an amount that can achieve the effects of the present invention.
  • the dose or amount used may vary according to the target species, body weight, sex, age, condition, or other factors. For example, it is 0.3 to 15 g as the fat of the invention.
  • the above formulations can be administered or used according to any dosage regimen, but can be administered or used once a day or more in divided doses for 1 day or more, preferably 7 days or more, more preferably 14 days or more, and even more preferably 30 days or more. It can be administered or used repeatedly and continuously for days or longer.
  • the preventive, therapeutic or ameliorating agent for inflammatory skin diseases of the present invention is preferably administered or used in the form of an oil composition.
  • the content of the fat of the present invention in the fat composition is preferably 90% by mass or more, from the viewpoint of usability. It is preferably 95% by mass or more, preferably 100% by mass or less, and more preferably 99.9% by mass or less.
  • the oil and fat composition preferably contains an antioxidant in terms of flavor, oxidation stability, coloration suppression, and the like.
  • the content of the antioxidant in the oil and fat composition is preferably 0.005% by mass or more and 1.0% by mass or less, more preferably 0.04% by mass or more, from the viewpoints of flavor, oxidation stability, coloration suppression, etc. It is 0.75% by mass or less, more preferably 0.08% by mass or more and 0.5% by mass or less.
  • Antioxidants are not particularly limited as long as they are used in foods, and include natural antioxidants, lecithin, tocopherol, ascorbyl palmitate, ascorbyl stearate, dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA). At least one selected from, etc. is preferable.
  • Subjects to whom the preventive, therapeutic or ameliorating agents for inflammatory skin diseases or the like of the present invention are administered or used include humans who desire prevention, treatment or improvement of inflammatory skin diseases, preferably atopic dermatitis, and skin barrier function. Humans, etc. who desire improvement can be mentioned. Examples of non-human animals include non-human mammals such as apes and other primates.
  • the present invention further discloses the following aspects.
  • ⁇ 1> Prevention of inflammatory skin diseases using, as an active ingredient, a fat containing 40% by mass or more of ⁇ -linolenic acid and 25% by mass or more of diacylglycerol in the fatty acids constituting the fat; A therapeutic or ameliorating agent.
  • a skin barrier function-improving agent comprising, as an active ingredient, a fat containing 40% by mass or more of ⁇ -linolenic acid and 25% by mass or more of diacylglycerol in the fatty acids constituting the fat.
  • a food for improving skin barrier function containing, as an active ingredient, a fat containing 40% by mass or more of ⁇ -linolenic acid and 25% by mass or more of diacylglycerol in the fatty acids constituting the fat.
  • the content of ⁇ -linolenic acid in the fatty acid constituting the fat is preferably 45% by mass or more, more preferably 50% by mass or more, still more preferably 52% by mass or more, and preferably 80% by mass. %, more preferably 70% by mass or less, more preferably 60% by mass or less, and 40% by mass or more and 80% by mass or less, preferably 45% by mass or more and 80% by mass or less, more preferably 50% by mass or more.
  • the content of linoleic acid (C18:2) in the fatty acid constituting the fat is preferably 5% by mass or more, more preferably 10% by mass or more, and preferably 40% by mass or less, more preferably is 30% by mass or less, more preferably 20% by mass or less, preferably 5% by mass or more and 40% by mass or less, more preferably 10% by mass or more and 30% by mass or less, still more preferably 10% by mass or more
  • the content of oleic acid (C18:1) in the fatty acid constituting the fat is preferably 10% by mass or more, and is preferably 50% by mass or less, more preferably 40% by mass or less, and still more preferably is 30% by mass or less, preferably 10% by mass or more and 50% by mass or less, more preferably 10% by mass or more and 40% by mass or less, still more preferably 10% by mass or more and 30% by mass or less ⁇ 1 > to the agent or food according to any one of ⁇ 6>.
  • the content of diacylglycerol in the oil is preferably 30% by mass or more, more preferably 50% by mass or more, still more preferably 55% by mass or more, still more preferably 60% by mass or more, and still more preferably 65% by mass.
  • the content of ⁇ -linolenic acid in the fatty acid constituting diacylglycerol is preferably 40% by mass or more, more preferably 45% by mass or more, still more preferably 50% by mass or more, and still more preferably 52% by mass or more.
  • 80% by mass or less more preferably 70% by mass or less, still more preferably 60% by mass or less, preferably 40% by mass or more and 80% by mass or less, more preferably 45% by mass or more 80% by mass or less, more preferably 50% by mass or more and 80% by mass or less, more preferably 50% by mass or more and 70% by mass or less, still more preferably 52% by mass or more and 70% by mass or less, still more preferably 52% by mass or more and 60% by mass % or less, the agent or food according to any one of ⁇ 1> to ⁇ 8>.
  • Inflammatory skin disease preferably atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, sebum-deficient eczema, erythema nodosum, neonatal acne/acne-like rash, eczema, hair Capsulitis, infantile eczema, or dry skin, more preferably atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, sebaceous eczema, or erythema nodosum, more preferably atopic
  • the agent or food according to any one of ⁇ 1>, ⁇ 3>, ⁇ 5> to ⁇ 9>, which is dermatitis.
  • the content of ⁇ -linolenic acid in fatty acids constituting fats and oils is 40% by mass or more, and the content of diacylglycerol is 25% by mass for producing an agent for preventing, treating, or improving inflammatory skin diseases. % or more.
  • the content of ⁇ -linolenic acid in fatty acids constituting fats and oils is 40% by mass or more, and the content of diacylglycerol is 25% by mass, for use in the prevention, treatment or improvement of inflammatory skin diseases. Fats and oils that are above.
  • the content of ⁇ -linolenic acid in fatty acids constituting fats and oils is 40% by mass or more and the content of diacylglycerol is 25% by mass or more.
  • Non-therapeutic use of certain oils is 40% by mass or more and the content of diacylglycerol is 25% by mass or more.
  • Inflammatory skin disease preferably atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, sebum-deficient eczema, erythema nodosum, neonatal acne/acne-like rash, eczema, hair Capsulitis, infantile eczema, or dry skin, more preferably atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, sebaceous eczema, or erythema nodosum, more preferably atopic
  • ⁇ 16> An oil containing 40% by mass or more of ⁇ -linolenic acid and 25% by mass or more of diacylglycerol in fatty acids constituting the oil for producing a skin barrier function improving agent. use.
  • Oils and fats having a content of ⁇ -linolenic acid of 40% by mass or more and a content of diacylglycerol of 25% by mass or more in fatty acids constituting the fats and oils for use in improving skin barrier function.
  • ⁇ 19> The oil or use according to any one of ⁇ 16> to ⁇ 18>, wherein the skin barrier function is preferably moisture permeation barrier function.
  • ⁇ 20> The fat or oil according to any one of ⁇ 12> to ⁇ 19>, wherein the content of ⁇ -linolenic acid in the fatty acid constituting the diacylglycerol is 40% by mass or more.
  • Inflammatory skin diseases preferably atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, sebum-deficient eczema, erythema nodosum, neonatal acne/acneiform eruption, eczema, hair Capsulitis, infantile eczema, or dry skin, more preferably atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, sebaceous eczema, or erythema nodosum, more preferably atopic
  • the method according to ⁇ 21> which is dermatitis.
  • ⁇ 23> Improving the skin barrier function by administering or applying to a subject an oil having a content of ⁇ -linolenic acid of 40% by mass or more and a content of diacylglycerol of 25% by mass or more in the fatty acids constituting the oil. How to improve.
  • ⁇ 24> The method according to ⁇ 23>, wherein the skin barrier function is preferably a moisture permeation barrier function.
  • ⁇ 25> The method according to any one of ⁇ 21> to ⁇ 24>, wherein the content of ⁇ -linolenic acid in the fatty acid constituting the diacylglycerol is 40% by mass or more.
  • Example 1 [Preparation of oil and special feed] Fatty acids obtained by enzymatically hydrolyzing linseed oil (manufactured by Archer Daniels Midland) were fractionated by cooling and centrifugation to obtain fractionated fatty acids. 300 parts by mass of the obtained fractionated fatty acid and 47 parts by mass of glycerin were mixed, and an esterification reaction was performed using a commercially available immobilized 1,3-position selective lipase (Novozyme) as a catalyst. After removing the immobilized enzyme by filtration, the reaction product was subjected to molecular distillation, followed by acid treatment and water washing to obtain a treated oil. After deodorizing the treated oil, an antioxidant was added to prepare a linseed oil-derived diacylglycerol (DAG)-containing oil (lin-DAG).
  • DAG linseed oil-derived diacylglycerol
  • the same antioxidant as lin-DAG was added to lin-TAG and soy-TAG at the same concentration.
  • AIN-93G Oriental Yeast Co., Ltd.
  • AIN-93G Used as mouse feed from which soybean oil (7% by mass) and cornstarch (3% by mass) originally contained are removed, and 10% by mass of any of the above fats and oils
  • Three types of special diets were prepared by addition.
  • Table 1 shows the glyceride and fatty acid compositions of lin-DAG, lin-TAG and soy-TAG.
  • the C18:3 unsaturated fatty acid in the fatty acid composition in Table 1 is ⁇ -linolenic acid.
  • Table 2 shows the fatty acid compositions of lin-DAG, lin-TAG and soy-TAG diacylglycerols.
  • the method for analyzing the fatty acid composition of diacylglycerol is as follows. After extracting and derivatizing the DAG fraction from each fat sample, it was analyzed by gas chromatography (GLC method) under the following conditions. At this time, the measurement method complied with American Oil Chemists' Society (AOCS) Official Method Ce 1f-96. The C18:3 unsaturated fatty acid in the fatty acid composition in Table 2 is ⁇ -linolenic acid.
  • Biosta AD ointment (Biosta Co., Ltd.) containing Dermatophagoides farinae-derived allergen was evenly applied to the back of the neck and auricle of the mice in the percutaneous sensitization group.
  • 150 ⁇ L of a 4 mass% sodium dodecyl sulfate (SDS) aqueous solution was evenly applied to the back of the neck and auricle of the mouse to induce rough skin, and then 100 mg of Biosta AD ointment was again applied to the same site. applied evenly.
  • SDS sodium dodecyl sulfate
  • the dermatitis score was evaluated according to each index in Table 3 below. Each index, i) redness/bleeding, (ii) crust formation/dryness, (iii) edema, (iv) abrasion/tissue loss, was evaluated, and the sum of the scores obtained was evaluated. The value (0-12 points) was taken as the final dermatitis score.
  • RNA expression analysis in the skin at the dermatitis-induced site was performed as follows. Total RNA was extracted from the collected cervical back skin using RNeasy Mini Kit (QIAGEN) according to the recommended protocol. cDNA was synthesized from the obtained total RNA using SuperScript TM VILO TM cDNA Synthesis Kit (Thermo Fisher Scientific) according to the recommended protocol. After that, by performing real-time PCR using the obtained cDNA, the expression analysis of mRNA of various cytokines contained in the skin of the dermatitis-induced disease site was performed.
  • mRNA expression levels were detected by preparing samples using Taqman TM Fast Universal PCR Master Mix (2 ⁇ ) (Applied Biosystems) and Taqman TM probes specific to each gene.
  • Taqman TM probes used in expression analysis of various cytokine genes are shown in Table 4 below.
  • RPLP0 was also used as an endogenous control.
  • cytokines are responsible for various conditions such as seborrheic dermatitis, contact dermatitis, psoriasis, sebaceous eczema, erythema nodosum, neonatal acne/acne-like rash, eczema, folliculitis, infantile eczema, and dry skin. It has been reported that it contributes to the inflammatory response and decreased barrier function in inflammatory skin diseases.
  • the oil of the present invention can be used for atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, sebum-deficient eczema, erythema nodosum, neonatal acne/acneiform eruption, eczema, It can be said to be useful as an agent for preventing, treating or improving various inflammatory skin diseases such as folliculitis, infantile eczema and dry skin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Epidemiology (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Toxicology (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • General Preparation And Processing Of Foods (AREA)

Abstract

L'invention concerne un agent de prévention, de traitement ou d'atténuation d'une maladie inflammatoire de la peau.　Cet agent pour la prévention, le traitement ou l'atténuation d'une maladie inflammatoire de la peau, a comme principe actif une graisse/huile dans laquelle la teneur en acide α-linolénique est supérieure ou égale à 40 % en masse et la teneur en diacylglycérol est supérieure ou égale à 25 % en masse des acides gras constituant la graisse/huile.
PCT/JP2022/037897 2021-10-13 2022-10-11 Agent pour la prévention, le traitement ou l'atténuation d'une maladie inflammatoire de la peau WO2023063322A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP22881017.2A EP4417200A1 (fr) 2021-10-13 2022-10-11 Agent pour la prévention, le traitement ou l'atténuation d'une maladie inflammatoire de la peau
CN202280068545.9A CN118119388A (zh) 2021-10-13 2022-10-11 炎症性皮肤疾病的预防、治疗或改善剂

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2021-168413 2021-10-13
JP2021168413 2021-10-13

Publications (1)

Publication Number Publication Date
WO2023063322A1 true WO2023063322A1 (fr) 2023-04-20

Family

ID=85987991

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2022/037897 WO2023063322A1 (fr) 2021-10-13 2022-10-11 Agent pour la prévention, le traitement ou l'atténuation d'une maladie inflammatoire de la peau

Country Status (5)

Country Link
EP (1) EP4417200A1 (fr)
JP (2) JP2023058457A (fr)
CN (1) CN118119388A (fr)
TW (1) TW202329926A (fr)
WO (1) WO2023063322A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06247849A (ja) * 1993-02-25 1994-09-06 Kao Corp 免疫増強剤
DE19843566A1 (de) * 1998-09-23 2000-03-30 Beiersdorf Ag Verwendung von Wirkstoffen, gewählt aus der Gruppe der 1,2-Diacylglycerole, zur Stärkung der Barrierefunktion der Haut
JP2002138296A (ja) 2000-08-08 2002-05-14 Kao Corp 油脂組成物
JP2006219454A (ja) * 2005-02-14 2006-08-24 Suntory Ltd 皮膚疾患経口治療または予防剤
JP2009084230A (ja) * 2007-10-01 2009-04-23 Idemitsu Kosan Co Ltd 炎症抑制剤
JP2018104684A (ja) * 2016-12-22 2018-07-05 花王株式会社 油脂組成物
JP2020147527A (ja) * 2019-03-13 2020-09-17 国立大学法人九州大学 ヒアルロン酸産生促進剤および保湿剤、コラーゲン産生促進剤および抗シワ剤、細胞賦活化剤、ならびに、メラニン産生抑制剤および美白剤

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06247849A (ja) * 1993-02-25 1994-09-06 Kao Corp 免疫増強剤
DE19843566A1 (de) * 1998-09-23 2000-03-30 Beiersdorf Ag Verwendung von Wirkstoffen, gewählt aus der Gruppe der 1,2-Diacylglycerole, zur Stärkung der Barrierefunktion der Haut
JP2002138296A (ja) 2000-08-08 2002-05-14 Kao Corp 油脂組成物
JP2006219454A (ja) * 2005-02-14 2006-08-24 Suntory Ltd 皮膚疾患経口治療または予防剤
JP2009084230A (ja) * 2007-10-01 2009-04-23 Idemitsu Kosan Co Ltd 炎症抑制剤
JP2018104684A (ja) * 2016-12-22 2018-07-05 花王株式会社 油脂組成物
JP2020147527A (ja) * 2019-03-13 2020-09-17 国立大学法人九州大学 ヒアルロン酸産生促進剤および保湿剤、コラーゲン産生促進剤および抗シワ剤、細胞賦活化剤、ならびに、メラニン産生抑制剤および美白剤

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
"Method for Preparation of Fatty Acid Methyl Esters", vol. 2, 1996, JAPAN OIL CHEMISTS' SOCIETY, article "Standard Methods for the Analysis of Fats, Oils, and Related Materials", pages: 1
ADALSTEINSSON JAKAUSHIK S ET AL., EXP DERMATOL., vol. 29, no. 5, May 2020 (2020-05-01), pages 481 - 489
BELGE K ET AL., F1000PRIME REP., vol. 6, 2 January 2014 (2014-01-02), pages 4
HANEL KH ET AL., INT J MOL SCI., vol. 14, no. 4, 26 March 2013 (2013-03-26), pages 6720 - 45
JEAN-MARC MAURETTE, OCL, vol. 15, no. 4, 2008, pages 257 - 261
LEE HY ET AL., MEDIATORS INFLAMM., vol. 2013, 2013, pages 916497
POLYCARPOU A ET AL., FRONT IMMUNOL., vol. 8, 13 March 2017 (2017-03-13), pages 233
XIAOHUI LIU, ET AL: "Exploring the Binding Proteins of Glycolipids with Bifunctional Chemical Probes", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, VOL. 55, N. 46, 7 November 2016 (2016-11-07), pages 14330 - 14334, XP055628145, Retrieved from the Internet <URL:https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fanie.201608827> [retrieved on 20191002], DOI: 10.1002/anie.201608827 *

Also Published As

Publication number Publication date
EP4417200A1 (fr) 2024-08-21
JP2023158146A (ja) 2023-10-26
TW202329926A (zh) 2023-08-01
CN118119388A (zh) 2024-05-31
JP2023058457A (ja) 2023-04-25

Similar Documents

Publication Publication Date Title
EP2918278A1 (fr) Extraits d&#39;algues contenant de la fucoxanthine et du fucoxanthinol
TWI331902B (fr)
EP0454102A2 (fr) Compositions d&#39;acides gras essentiels
JPH0369886B2 (fr)
JP2018518451A (ja) 最適化された栄養分の脂肪酸組成
US11819486B2 (en) Composition for external use on skin for inflammatory diseases
EP2272383A1 (fr) Composition comportant des acides gras Omega-7 et/ou Omega-4
WO2023109290A1 (fr) Composition contenant de l&#39;huile microbienne et de l&#39;huile végétale et son utilisation
JP7520175B2 (ja) 血中デカン酸濃度の上昇方法、血中デカン酸濃度上昇剤、医薬組成物、食品組成物
WO2023063322A1 (fr) Agent pour la prévention, le traitement ou l&#39;atténuation d&#39;une maladie inflammatoire de la peau
JP5711616B2 (ja) Ｉｌ−１７産生抑制剤
WO2023063321A1 (fr) Agent antiallergique
JP2024150429A (ja) 皮膚状態改善剤
JP5099946B2 (ja) 抗腫瘍組成物の製造方法
JP2024051305A (ja) 糖質燃焼促進剤
JP6203320B2 (ja) 皮膚疾患経口治療または予防剤
JP7356833B2 (ja) 末梢体温亢進剤
JP4359205B2 (ja) 皮膚保湿用食品
JP2019019069A (ja) 体脂肪低減剤
JP2024150428A (ja) アレルギー症状抑制剤
JP2012082226A (ja) 皮膚疾患経口治療または予防剤
CN110038131B (zh) 一种烧创伤皮肤细胞修复的结构脂质组合物及其应用
KR20240114326A (ko) 식물 복합추출물을 유효성분으로 포함하는 항염증용, 항산화용 및 근 기능 개선용 조성물
JP6214474B2 (ja) 皮膚疾患経口治療または予防剤
Mohanan et al. NUTRITIONAL AND HEALTH BENEFITS OF COCONUT OIL

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22881017

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 18699471

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 202280068545.9

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 2022881017

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2022881017

Country of ref document: EP

Effective date: 20240513